LIXTE Biotechnology Holdings, Inc. (Nasdaq: LIXT) announced today the publication of new pre-clinical data revealing the metabolic pathway of its lead clinical compound LB-100, providing critical insights that could enhance patient selection for cancer treatment. The findings, published in BioXriv and the International Journal of Pharmaceutics, demonstrate how LB-100 converts to its active form, endothall, a protein phosphatase (PP2A) inhibitor shown to be effective in cancer treatment when combined with immunotherapy.
Researchers at the Netherlands Cancer Institute, led by Professor Rene Bernards, discovered a specific enzyme that mediates the conversion of LB-100 into endothall. This enzyme could serve as a potential biomarker to identify patients most likely to respond to LB-100 therapy, representing a significant advancement in the company's precision medicine approach.
"Clinical trials with LB-100 currently are underway for treatment of ovarian cancer and colorectal cancer," said Bas van der Baan, LIXTE's Chief Executive Officer. "The latest pre-clinical data provide a better understanding of the underlying biological availability of LB-100 and endothall in patients, and will help us in optimizing patient selection for future clinical trials."
Dual Conversion Pathways Identified
The research revealed two distinct pathways for LB-100 conversion to its active form. Scientists at BioPharmaWorks LLC, a LIXTE consultant, demonstrated that LB-100 can spontaneously convert into endothall through hydrolysis, though this process occurs slowly under physiological conditions.
More significantly, the Bernards laboratory identified an enzymatic conversion pathway that expedites the activation of LB-100 inside cells. This discovery explains how the drug achieves its therapeutic effects and provides a potential mechanism to predict which patients might benefit most from treatment.
Implications for Cancer Treatment
LB-100 represents a first-in-class PP2A inhibitor that has shown promising results in early clinical testing. The compound is well-tolerated in cancer patients at doses associated with anti-cancer activity and has demonstrated potential to significantly improve outcomes for patients undergoing various chemotherapies or immunotherapies.
The drug is part of LIXTE's pioneering effort in an emerging field of cancer biology called "activation lethality," which represents a novel treatment paradigm. According to the company, LB-100 has no known competitors and is protected by a comprehensive patent portfolio.
Ongoing Clinical Development
LIXTE is currently conducting proof-of-concept clinical trials with LB-100, focusing on ovarian cancer and colorectal cancer. The new findings regarding the drug's metabolism and activation will likely influence the design of future clinical studies and help identify which patients might benefit most from this treatment approach.
The biomarker strategy emerging from this research aligns with the growing trend toward personalized medicine in oncology, where treatments are increasingly matched to patients based on molecular and genetic characteristics of their tumors or metabolic profiles.
About LIXTE Biotechnology
LIXTE Biotechnology Holdings, Inc. is a clinical-stage pharmaceutical company focused on developing novel cancer therapies. The company's approach centers on targeting protein phosphatase 2A (PP2A), a key regulatory enzyme in cellular signaling pathways. By inhibiting PP2A with compounds like LB-100, LIXTE aims to enhance the effectiveness of standard cancer treatments and overcome treatment resistance.
The company continues to advance its pipeline while exploring the potential applications of LB-100 across various cancer types and treatment combinations. With these new insights into the drug's metabolism, LIXTE is positioned to refine its clinical development strategy and potentially accelerate the path toward more effective targeted cancer therapies.
